Epstein–Barr Virus


Epstein–Barr virus (EBV) is a ubiquitous gamma herpesvirus aetiologically linked to different lymphoid and epithelial malignancies and a number of systemic autoimmune diseases. The virus has a unique ability to transform resting B lymphocytes in vitro by expressing a set of latent genes, subsets of which are present in EBV‐associated tumours. EBV exploits the physiology of normal B‐cell differentiation to persist within the memory B‐cell pool of the immunocompetent host with strong T‐cell responses important for controlling EBV infection. Immunosuppressed transplant recipients and human immunodeficiency virus (HIV)‐infected individuals are at increased risk of developing EBV‐transformed B‐cell proliferations which often present as monoclonal non‐Hodgkin lymphomas. The major EBV‐associated tumours (Burkitt lymphoma, Hodgkin lymphoma and nasopharyngeal carcinoma) show restricted forms of latent viral gene expression reflecting a more complex pathogenesis involving additional cofactors. A number of pharmacological and immunotherapeutic approaches are being developed to treat or prevent these EBV‐associated tumours.

Key Concepts

  • Epstein–Barr virus (EBV) infection is implicated in the aetiology of several different lymphoid and epithelial malignancies, as well as a number of systemic autoimmune diseases.
  • EBV exploits the physiology of normal B‐cell differentiation to persist within the memory B‐cell pool of the immunocompetent host.
  • EBV‐encoded latent genes induce B‐cell transformation in vitro by altering cellular gene transcription and constitutively activating key cell signalling pathways.
  • Immunosuppressed transplant patients are at risk of developing EBV‐transformed B‐cell proliferations presenting as B‐cell lymphomas.
  • Other EBV‐associated tumours display more restricted forms of latent gene expression, reflecting more complex pathogenesis involving additional cofactors.
  • EBV sequence variation may reflect disease risk.
  • Pharmacological and immunotherapeutic approaches are being developed to treat or prevent EBV‐associated tumours.
  • More direct vaccine approaches are being examined for the treatment and prevention of EBV‐associated diseases.

Keywords: herpesvirus; B cells; latency; lymphoma; carcinoma; leiomyosarcoma; autoimmune diseases; vaccine; sequence variation; micro‐RNAs

Figure 1. Electron micrograph of the Epstein–Barr virus (EBV) virion.
Figure 2. EBV primary infection and persistence. Figure showing putative in vivo interactions between EBV and host cells. (a) Primary infection. EBV replicates in epithelial cells and spreads to lymphoid tissues as a latent growth‐transforming (latency III) infection of B cells. Many infected B cells are removed by emerging EBV‐specific T‐cell response. Some infected cells escape by downregulating EBV latent genes to establish a stable pool of resting virus‐positive memory B cells. (b) Persistent infection. EBV‐infected memory B cells become subject to the physiological controls governing memory B‐cell migration and differentiation. Occasional recruitment into germinal centre (GC) reactions resulting in activation of different EBV latency programmes and reentry into the memory cell reservoir or plasma cell differentiation with activation of virus lytic cycle. Infectious virions then initiate foci of EBV replication in epithelial cells and also new growth‐transforming infection of naïve and/or memory B cells. For more detailed explanations, see Young and Rickinson and Thorley‐Lawson and Gross . Reproduced from Mahy and Van Regenmortel 2008 © Elsevier.
Figure 3. EBV genome forms. (a) The episome, in which the EBV genome circularises via the terminal repeats (TR), is the hallmark of EBV latency. EBNA1 is the principal EBV latency protein. EBNA promoters are shown (Cp, Wp, Qp), as well as the EBNA1 open reading frame (triangle). Shaded circles represent the two areas of the EBV genome where EBNA1 dimers bind. Two binding sites are found in the Q locus, whereas 24 binding sites are found within the plasmid origin of replication (ori‐P). EBNA‐1 activates ori‐P and autoregulates Qp. (b) The linear EBV genome is diagnostic of productive infection. The positions of terminal (TR) and internal direct (IR) repeat units are shown. Regions of unique sequence are designated U. Latent and lytic (ori‐lyt) origins of DNA (deoxyribonucleic acid) replication are shown as open circles. Arrows pointing rightward or leftward indicate the location and direction of transcription of the coding sequences of the EBV genes mentioned in the text.


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Further Reading

Kieff E and Rickinson AB (2006) Epstein–Barr virus and its replication. In: Knipe DM and Howley PM (eds) Fields Virology, 5th edn. Philadelphia, PA: Lippincott Williams and Wilkins Publishers.

Kuppers R (2005) Mechanisms of B cell lymphoma pathogenesis. Nature Reviews. Cancer 5: 251–262.

Kutok JL and Wang F (2006) Spectrum of Epstein–Barr virus‐associated diseases. Annual Review of Pathology: Mechanisms of Disease 1: 375–404.

Rickinson AB and Kieff E (2006) Epstein–Barr virus. In: Knipe DM and Howley PM (eds) Fields Virology, 5th edn. Philadelphia, PA: Lippincott Williams and Wilkins Publishers.

Robertson ES (ed) (2005) Epstein–Barr Virus. Norfolk, UK: Caister Academic Press.

Tao Q, Young LS, Woodman CB and Murray PG (2006) Epstein–Barr virus and its associated cancers – genetics, epigenetics, pathobiology and novel therapeutics. Frontiers in Bioscience 11: 2672–2713.

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Morris, Mhairi A(Jun 2017) Epstein–Barr Virus. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001020.pub3]